In the sixth blog of our special series on Evidently Cochrane: “Oh, really?” 12 things to help you question health advice, Lynda Ware, a Senior Fellow in General Practice at Cochrane UK, explains why detecting diseases earlier by screening is not always beneficial, and may – in some cases – be harmful.
Surely sooner is always better?
It seems counterintuitive that detecting diseases earlier by screening might not always be beneficial, and might, in some cases, actually cause harm.
Unfortunately, it’s true…
What is screening?
Screening programmes are designed to identify those most at A way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of having or developing a disease. Screening looks for risk markers of disease in people who otherwise feel entirely well. It is this that differentiates it from a diagnostic test, which is carried out in someone suspected of already having a disease.
Examples of screening programmes include: mammography for breast cancer; the PSA blood test for prostate cancer; cholesterol and blood pressure measurements to prevent heart attacks and strokes; the heel-prick test for phenylketonuria in newborn babies.
There are certain basic principles which underpin an appropriate screening test:
- The condition being screened is serious and/or affects large numbers of people
- The condition has a recognisable early stage, which when treated can significantly improve the outcome of the condition
- There is effective, safe Something done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes. for the condition
- There is a test which can accurately identify the condition, with few false negatives (missed cases) and few false positives (false alarms)
- The benefits of screening should outweigh any harms it might cause. Harms can be physical (e.g. radiation exposure from scanning) and psychological (e.g. anxiety and distress whilst waiting for results to return – especially if ultimately found to be clear).
- Screening should be cost effective
Some success stories
Let’s start with some screening programmes that have proved beneficial.
This is an inborn error of metabolism, which untreated can lead to serious irreversible brain damage. It affects around 1 in 10000 babies born in the UK. Special diets can help ensure normal development. A heel-prick screening blood test is routinely performed on newborn infants about five days after birth to test for PKU (and other conditions).
Risk factors for heart attacks and strokes
There is good evidence that high blood pressure, raised cholesterol levels and tobacco smoking are risk factors for cardiovascular disease. Identifying, advising and treating people with such risk factors helps prevent heart attacks and strokes.
Diabetic eye disease
Annual screening is offered to all people with diabetes aged 12 and over to pick up and treat associated eye problems early.
A screening programme that was stopped
Sometimes screening programmes can cause harm.
This is a rare childhood cancer, affecting nerve cells, in which the five year survival rate is 43% in children aged one to four years. Survival rates are affected by age at diagnosis, which part of the body is affected and how far the tumour has spread. In some cases, the tumour disappears completely without treatment.
In 1985 mass screening for neuroblastoma was introduced in Japan. It was stopped in 2004 when it became apparent that screening did not reduce the numbers of children dying from the disease. In addition, children with tumours that would never have produced symptoms, and which would have gone away without treatment, underwent unnecessary surgery and chemotherapy.
“Screening for neuroblastoma illustrates how easily one can fall into the trap of assuming that because a disease can be detected early, screening must be worthwhile . . . The two studies demonstrate how neuroblastoma screening was not only worthless, but led to “over-diagnosis” and must have identified tumours that would have spontaneously regressed. Both studies mentioned children in the screened group suffering severe complications due to the treatment . . . Hopefully these lessons will be learned when considering the implementation of other screening programmes – for example screening for prostate cancer.” – Morris JK. Screening for neuroblastoma in children.
Where screening is less straightforward
Prostate cancer screening
This blood test measures prostate-specific antigen (PSA), which is raised in most men with prostate cancer.
Unfortunately, the test has serious limitations as a screening tool but this hasn’t prevented widespread promotion by professional and patient groups and by companies selling the test.
Why does it fall short?
“The screening process is like passing people through a sieve. The holes in the screening sieve are a certain size that will catch some people and allow others to pass through. A screening test is designed to catch people who are at risk of a disease (it must be very sensitive) and allow those not at risk to pass through (it must be very specific).
Sometimes people will get stuck in the sieve who will turn out not to be at risk i.e. false alarms. Others will pass through the sieve despite being at risk i.e. missed cases (false negatives). Everyone picked up in the sieve will go on for more testing to determine if they have the disease and need treatment.” – Angela Raffle
- False negatives: the PSA test may be normal in 1 in 7 men who do have prostate cancer – meaning these cases would be missed
- False positives: There are several conditions, not related to cancer, that can cause the PSA to be raised e.g. age, vigorous exercise, prostatitis, urine infection, some medications. These men would be told – wrongly – that they have cancer.
- It does not differentiate between slow-growing and fast-growing prostate cancers (the so-called ‘pussycats and tigers’). Most men do not have aggressive tumours – they die with it, not because of it.
More prostate cancers are being diagnosed as a result of screening and testing but many of these would not be life-threatening. Treatment, however, can be life-altering with some men suffering impotence and urinary incontinence as side-effects of treatment.
“Prostate cancer screening did not significantly decrease prostate cancer-specific death (or overall mortality) in a combined The use of statistical techniques in a systematic review to combine the results of included studies. Sometimes misused as a synonym for systematic reviews, where the review includes a meta-analysis. of five RCTs [Randomization is the process of randomly dividing into groups the people taking part in a trial. One group (the intervention group) will be given the intervention being tested (for example a drug, surgery, or exercise) and compared with a group which does not receive the intervention (the control group). controlled trials]. Harms associated with PSA-based screening and subsequent diagnostic evaluations are frequent and moderate in severity. Overdiagnosis and overtreatment are common and are associated with treatment-related harms. Men should be informed of this and the demonstrated adverse effects when they are deciding whether or not to undertake screening for prostate cancer. Any reduction in prostate cancer-specific mortality may take up to 10 years to accrue; therefore, men who have a life expectancy less than 10 to 15 years should be informed that screening for prostate cancer is unlikely to be beneficial”. – the conclusions of a 2013 Cochrane Review ‘screening for prostate cancer’.
Where does that leave us? How do we decide whether to be screened or not?
Many screening tests are available on the NHS and privately. It is really important to understand why the test is being offered, what its limitations are and what the Outcomes are measures of health (for example quality of life, pain, blood sugar levels) that can be used to assess the effectiveness and safety of a treatment or other intervention (for example a drug, surgery, or exercise). In research, the outcomes considered most important are ‘primary outcomes’ and those considered less important are ‘secondary outcomes’. might be. Life isn’t simple and the issues surrounding some screening tests certainly aren’t. Discuss with your doctor the benefits and harms of screening, remembering that earlier detection of a disease is not necessarily better.
Join in the conversation on Twitter with @CochraneUK and @lynda_ware or leave a comment on the blog. Please note, we cannot give medical advice and we will not publish comments that link to commercial sites or appear to endorse commercial products. We welcome diverse views and encourage discussion. However we ask that comments are respectful and reserve the right to not publish comments we consider offensive.
Visit the Teachers of Evidence-Based Health Care website, where you can find resources which explain and illustrate that earlier detection of disease is not necessarily better.
Read the rest of the blogs in the series: “Oh, really?” 12 things to help you question health advice.
Lynda Ware has nothing to disclose.